Letters to the Editor / International Journal of Antimicrobial Agents 40 (2012) 562– 573 567

Table 1Minimum inhibitory concentrations (MICs) and characteristics of the five NDM-producing Enterobacteriaceae.

Patient No. Organism MIC (�g/mL) Modified Hodge test EDTA disk synergy test GenBank accession no.

IPM ETP

1 Klebsiella pneumoniae >32 >32 +/− IPM(+) JN656098Escherichia coli >32 >32 + IPM(+) JN656099Proteus mirabilis 32 >32 +/−

2 Providencia rettgeri >32 >32 + IPM(+) JN656097−

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3 Morganella morganii >32 1.0

PM, imipenem; MEM, meropenem; EDTA, ethylene diamine tetra-acetic acid.

In conclusion, we report three NDM-1 cases from Israel. Allatients had complicated diabetes and received broad-spectrumntibiotic treatments. The cases were not related to each other,nd none of the cases had a travel history. Detection of theserganisms requires special notice and they may be more abundanthan thought.

cknowledgments

The authors thank the staff of the National Center for Infectionontrol (Israel) for their expert help.

Funding: No funding sources.Competing interests: None declared.Ethical approval: Not required.

eferences

1] Yong D, Toleman MA, Giske CG, Cho HS, Sundman K, Lee K, et al. Characteriza-tion of a new metallo-�-lactamase gene, blaNDM-1, and a novel erythromycinesterase gene carried on a unique genetic structure in Klebsiella pneumo-niae sequence type 14 from India. Antimicrob Agents Chemother 2009;53:5046–54.

2] Kumarasamy KK, Toleman MA, Walsh TR, Bagaria J, Butt F, Balakrishnan R, et al.Emergence of a new antibiotic resistance mechanism in India, Pakistan, andthe UK: a molecular, biological, and epidemiological study. Lancet Infect Dis2010;10:597–602.

3] Nordmann P, Poirel L, Walsh TR, Livermore DM. The emerging NDM carbapene-mases. Trends Microbiol 2011;19:588–95.

4] Espinal P, Fugazza G, López Y, Kasma M, Lerman Y, Malhotra-Kumar S, et al. Dis-semination of an NDM-2-producing Acinetobacter baumannii clone in an Israelirehabilitation center. Antimicrob Agents Chemother 2011;55:5396–8.

5] Diene SM, Bruder N, Raoult D, Rolain JM. Real-time PCR allows detection of theNew Delhi metallo-�-lactamase (NDM-1)-encoding gene in France. Int J Antimi-crob Agents 2011;37:544–6.

Tamar LachishMeital Elimelech

Natalie ArieliShaare-Zedek Medical Center, P.O.B. 3235, 91031 Jerusalem, Israel

Amos AdlerNational Center for Infection Control, Ministry of Health, Israel

Jean-Marc Rolain ∗

Unité de Recherche sur les Maladies Infectieuses et TropicalesEmergentes (URMITE), UMR CNRS-IRD-INSERM, IHU Méditerranée

Infection, Aix-Marseille Université, 27 Bd Jean Moulin, 13385Marseille cedex 05, France

Marc Victor Assous ∗

Microbiology and Immunology Laboratory, Shaare-Zedek MedicalCenter, Jerusalem, Israel

∗ Corresponding authors.E-mail addresses: jean-marc.rolain@univ-amu.fr (J.-M. Rolain),

mvassous@gmail.com (M.V. Assous)

16 July 2012oi:10.1016/j.ijantimicag.2012.07.011

IPM(+), MEM(+) JN656100

Comparative in vitro activities of daptomycin, vancomycin,teicoplanin and linezolid against resistant Gram-positive bac-terial isolates from two large centres in western India

Sir,

Skin and soft-tissue infections (SSTIs) caused by Staphylococcusaureus are a major cause of mortality and morbidity in hospi-talised patients. Vancomycin (VAN) and teicoplanin (TEIC) arewidely used in the treatment of SSTIs, but their clinical use islimited due to increasing in vitro minimal inhibitory concentra-tions (MICs). Moreover, linezolid (LNZ) and daptomycin (DAP),approved by the US Food and Drug Administration (FDA), havebeen reported to be more effective and safe in treating SSTIs.Thus, this study aimed to compare the antimicrobial activity ofDAP and LNZ in comparison with VAN and TEIC against resis-tant Gram-positive isolates, including meticillin-resistant S. aureus(MRSA), meticillin-resistant coagulase-negative staphylococci(MR-CoNS) and ampicillin-resistant enterococci (ARE), culturedfrom patients diagnosed with SSTIs and bloodstream infections(BSIs).

A total of 160 hospitalised individuals diagnosed with SSTIsand/or BSIs due to resistant Gram-positive organisms cultured fromclinical specimens such as blood, pus, abscesses, tissues and woundswabs were considered for this analysis. All specimens were pro-cessed for microbial culture and species identification (MR-CoNS,MRSA and Enterococcus spp.) as per Clinical and Laboratory Stan-dards Institute (CLSI) guidelines [1]. Antimicrobial susceptibilitytesting for VAN, TEIC, LNZ and DAP was performed using Etest strips(AB BIODISK, Solna, Sweden) and result interpretation was done asper CLSI guidelines [1].

A total of 160 clinical isolates (80 MRSA, 35 MR-CoNSand 45 ARE) were collected from February–August 2010. DAPshowed high in vitro activity against MR-CoNS (100% suscep-tibility; mean MIC = 0.253 �g/mL), MRSA (93.75% susceptibility;mean MIC = 0.199 �g/mL) and ARE (93.3% susceptibility; meanMIC = 1.770 �g/mL) (Fig. 1). A total of 8 isolates (5%) were non-susceptible to DAP, comprising 5 MRSA isolates [MICs = 1.5 �g/mL(n = 1), 2 �g/mL (n = 2), 3 �g/mL (n = 1) and 6 �g/mL (n = 1)] and 3ARE [MICs = 6 �g/mL (n = 2) and 8 �g/mL (n = 1)].

VAN showed high in vitro activity against MR-CoNS (100%susceptibility; mean MIC = 1.471 �g/mL), MRSA (100% susceptibil-ity; mean MIC = 1.243 �g/mL) and ARE (77.7% susceptibility; meanMIC = 1.264 �g/mL). A total of 9 ARE isolates (20%) were resistantto VAN [MICs = 32 �g/mL (n = 1) and ≥256 �g/mL (n = 8)] and 1 AREisolate (2.2%) (MIC = 16 �g/mL) showed intermediate susceptibilityto VAN.

TEIC was highly active against CoNS (97.1% susceptibil-ity; mean MIC = 2.066 �g/mL), MRSA (100% susceptibility;mean MIC = 0.971 �g/mL) and ARE (77.7% susceptibility; mean

MIC = 0.670 �g/mL). A total of 5 isolates (3.1%) showed interme-diate susceptibility; 1 CoNS isolate (MIC = 12 �g/mL) and 4 AREisolates [MICs = 12 �g/mL (n = 1), 16 �g/mL (n = 2) and 24 �g/mL(n = 1)]. Also, 6 ARE isolates (3.8%) were reported to be resistant

568 Letters to the Editor / International Journal of Antimicrobial Agents 40 (2012) 562– 573

Fig. 1. Minimal inhibitory concentrations (MICs) for each meticillin-resistant coagulase-negative staphylococci (MR-CoNS), meticillin-resistant Staphylococcus aureus (MRSA)and ampicillin-resistant enterococci (ARE) isolate to daptomycin (DAP), vancomycin (VAN), teicoplanin (TEIC) and linezolid (LNZ). – – – indicates the susceptibility breakpointo L, wh(

[(

frobLshitpHmHta

LacrtI

McM4(MwamT

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f each drug for each organism (the breakpoint of LNZ for Staphylococcus spp. is 4 �g/mdata not shown).

MICs = 32 �g/mL (n = 1), 48 �g/mL (n = 4) and ≥256 �g/mLn = 1)].

All isolates showed 100% susceptibility to LNZ; the mean MICsor MR-CoNS, MRSA and ARE were 0.488, 0.672 and 0.817 �g/mL,espectively. The above results indicate that a high proportionf isolates were found to be susceptible to all four antimicro-ial agents: VAN and TEIC showed higher MICs than DAP andNZ. DAP showed better but comparable efficacy in compari-on with LNZ against staphylococcal spp., but reports a two-foldigher MIC against ARE isolates. Also, all DAP-non-susceptible

solates reported a mean 4.537-fold higher MIC value thanhat reported by LNZ; thus, in such cases LNZ would be thereferred choice for treating resistant Gram-positive infections.owever, there have also been reports of favourable treat-ent outcomes with DAP in patients failing LNZ treatment [2].ence, the choice of the drug for treatment would be a mat-

er of individual clinical experience and the individual isolate’sntibiogram.

These study findings confirm the good in vitro activity ofNZ (mean MIC = 0.672 �g/mL) and DAP (mean MIC = 0.829 �g/mL)gainst resistant Gram-positive isolates. LNZ reported 100% sus-eptibility of staphylococcal and enterococcal spp., whilst DAPeported 95.65% (110/115) of the staphylococcal spp. to be suscep-ible at a MIC of 1 �g/mL, a finding similar to another study fromndia [3].

VAN also reported 100% susceptibility (meanIC = 1.313 �g/mL) of staphylococcal spp., but at a MIC higher in

omparison with DAP (mean MIC = 0.333 �g/mL) and LNZ (meanIC = 0.616 �g/mL). Further analysis revealed that VAN reported

8.75% of isolates (39/80) with a MIC > 1 �g/mL, of which 10.3%4/39) isolates reported a MIC of 2 �g/mL, indicating an increasing

IC creep; thus, in such cases the recommended VAN dosages

ould have no clinical impact and other drugs could be considered

s a better treatment option [4]. TEIC reported a lower but similarean MIC (2.990 �g/mL) in comparison with VAN (3.263 �g/mL).

hese results are in concordance to another study where the mean

[

ich is not depicted in the graph). Seven ARE isolates reported a VAN MIC > 256 �g/mL

TEIC MIC (2.1 �g/mL) was found to be lower than that of VAN(2.3 �g/mL) [5].

In addition, 20 methicillin-susceptible S. aureus isolates werealso evaluated, reporting a mean MIC higher than DAP (1.425 �g/mLvs. 0.277 �g/mL; data not shown).

In conclusion, DAP and LNZ could be used as alternative drugsfor the treatment of SSTIs caused by resistant Gram-positiveorganisms.

Acknowledgments

The authors thank the National Health and Education Societyand P.D. Hinduja National Hospital and Medical Research Centre(Mumbai, India) for their encouragement and support.

Funding: Etest strips were provided by Novartis (Mumbai, India).Competing interests: None declared.Ethical approval: Ethical approval was obtained by Hinduja Hos-

pital (Mumbai, India) from the National Health and EducationSociety (523-10-CR). Tata Memorial Hospital has applied for anethical approval.

References

1] Clinical and Laboratory Standards Institute. Performance standards for antimi-crobial susceptibility testing: twenty-first informational supplement. DocumentM100-S21. Wayne, PA: CLSI; 2011.

2] Antony SJ, Tiscareno-Grajeda I, Misenhiemer G, Heyderman J. Use of dapto-mycin in the treatment of prosthetic joint infections: a prospective observationalstudy of 30 patients with infected prosthetic joint infections. Internet J Infect Dis2009:7, http://dx.doi.org/10.5580/1479.

3] Behera B, Jain N, Sharma S, Mathur P, Misra MC. Antimicrobial activ-ity of daptomycin against Staphylococcus aureus isolates from skinand skin structure infections of trauma patients. J Infect 2010;61:195–6.

4] Rybak MJ, Lomaestro BN, Rotschafer JC, Moellering RC, Craig WA, Billeter M, et al.Vancomycin therapeutic guidelines: a summary of consensus recommendationsfrom the Infectious Diseases Society of America, the American Society of Health-System Pharmacists, and the Society of Infectious Diseases Pharmacists. ClinInfect Dis 2009;49:325–7.

al of Antimicrobial Agents 40 (2012) 562– 573 569

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5] Pasticci MB, Moretti A, Stagni G, Ravasio V, Soavi L, Raglio A, et al. Bactericidalactivity of oxacillin and glycopeptides against Staphylococcus aureus in patientswith endocarditis: looking for a relationship between tolerance and outcome.Ann Clin Microbiol Antimicrob 2011;10:26.

Sanjay BiswasTata Memorial Hospital, Parel, Mumbai 400012, India

Jaya WatwaniViral VadwaiAnjali Shetty

P.D. Hinduja National Hospital and Medical Research Centre, Mahim,Mumbai 400016, India

Rohini KelkarTata Memorial Hospital, Parel, Mumbai 400012, India

Camilla Rodrigues ∗

P.D. Hinduja National Hospital and Medical Research Centre, Mahim,Mumbai 400016, India

∗ Corresponding author. Present address: P.D. Hinduja NationalHospital and Medical Research Centre, 5th Floor, S1 (Lalita

Girdhar) Building, Microbiology Department, Veer Savarkar Marg,Mahim, Mumbai 400016, India. Tel.: +91 22 2444 7795;

fax: +91 22 2444 2318.E-mail address: dr crodrigues@hindujahospital.com (C. Rodrigues)

14 May 2012oi:10.1016/j.ijantimicag.2012.07.013

ntimicrobial susceptibility of an emergent zoonotic pathogen,rcobacter butzleri

ir,

The increasing isolation rate of Arcobacter spp. from a wideange of sources worldwide as well as antimicrobial resis-ance trends among these species have increased their clinicalmportance. Infections caused by Arcobacter spp. are usually self-imiting but in cases of severe and chronic conditions, properreatment is required [1,2]. This study aimed to determine thentimicrobial susceptibility of Arcobacter butzleri and to calcu-ate the MIC50 and MIC90 values, corresponding to the antibioticoncentration inhibiting ≥50% or ≥90% of the isolates, respec-ively.

Assessment of antimicrobial resistance of 46 A. butzleri iso-ates originating from cattle (n = 6), beef (n = 29), milk (n = 5), watern = 3) and environmental surfaces (n = 3) was performed againstommonly used antibiotics (Table 1) using M.I.C.EvaluatorTM

M.I.C.E.TM) strips as described by the manufacturer (Oxoid Ltd.,asingstoke, UK) as well as by the disk diffusion method as rec-mmended by the Clinical and Laboratory Standards InstituteCLSI) [3]. Classification of isolates as resistant was based onreakpoint values recommended for Enterobacteriaceae [3], exceptor the minimum inhibitory concentration (MIC) breakpoints ofmpicillin and cefotaxime, which were adopted from the CLSI4] as recommended for Campylobacter. Tests were performed inuplicate and mean values were calculated to report the results.scherichia coli ATCC 25922, Staphylococcus aureus ATCC 25923nd S. aureus CCUG 15915 were used as quality control organ-sms.

Arcobacter isolates were highly resistant to ampicillin (M.I.C.E.,3.9%; disk diffusion. 78.3%), followed by cefotaxime (M.I.C.E.,

9.6%; disk diffusion, 65.2%) and erythromycin (M.I.C.E., 69.6%;isk diffusion, 45.7%). Resistance in Arcobacter to �-lactam antibi-tics is mediated by the lrgAB operon or �-lactamase genes thatlter the penicillin-binding protein sites [2]. Cefotaxime has never Ta

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